Brain tumours - Identification of common therapeutic targets in schwannomas and meningiomas

COMPLETED PROJECT OVERVIEW

Plymouth University - Professor Oliver Hanemann

This research on schwannomas and meningiomas used a unique human cell culture model using cells derived from surgical patients. This has led to the identification and testing of new, targeted therapies and the team have successfully translated their research into early clinical trials. This approach has allowed them to screen approved drugs directly and go straight into clinical trials, avoiding pre-clinical animal trials.

PROJECT OUTCOMES

Meningiomas and schwannomas are primary brain tumours affecting brain and spinal cord. Meningiomas in particular are amongst the most common brain tumours. They are usually not aggressive; however, when becoming symptomatic the only available treatment is surgical resection or radiotherapy, which can leave patients with mild to severe morbidity. Meningiomas and schwannomas can grow simultaneously in patients affected by the genetic condition Neurofibromatosis type 2, which predispose them to a continuous recurrence of these tumours. No pharmaceutical treatment is available to treat these patients, so new therapeutic strategies are urgently needed.

The aim of this project was the identification of novel specific and/or common therapeutic targets in meningiomas and schwannomas by using a proteomic approach.

It is well known that tumours originate because the accumulation of several mutations that occurs on the control centre of our cells, the DNA. The DNA codifies all the information in the body; the colour of the eyes, the shape of the nails, the tone of the skin, etc. and most importantly it defines the behaviour of the different cells in the different compartments of our body. When this information is not produced correctly the cell becomes ‘confused’ and, when the cell is able to survive to this ‘confused state’, it starts to grow without control thus generating a tumour mass.

In decades of research scientists have been able to characterized most of the mutations that affect the DNA and that are responsible for the tumour growth. This has been very well studied also in meningiomas and schwannomas, but, despite we know the reasons why these tumours are growing, this information is not sufficient to find an effective therapy.

Indeed, the drugs commonly used in chemotherapy are not capable of attaching the DNA at the specific injured sites that cause the cell to be ‘confused’ but they attack the proteins.

Proteins are the effectors of the information codified by the DNA, they are the cellular workers that obey to the orders given by the DNA, and most importantly they are drugable.

Cancer therapy is moving towards a more selective and efficient approach that is defined ‘molecular targeted therapy’. Tumour cells differ from heathy cells in the content of proteins, in particular, some proteins can be highly present in the tumour cells but barely present in heathy cells and this feature confers the protein the title of ‘therapeutic target’. A drug capable of specifically target a protein localised mainly on tumour cells it would be highly specific and effective against the tumour, at the same time preserving the healthy tissue from the side effects of the drug.

In this context we analysed the protein content of schwannomas and meningiomas and compared it to the healthy cells where the tumour originates from. We identified hundreds of differences, thus defining the signature of these tumours. Some proteins were highly present only in one tumour type but not in the other; however, few proteins where found in both tumour types but much less in the healthy cells.

We confirmed that the targets we are currently working on are responsible for an increased cellular proliferation, meaning that therapeutically targeting these proteins can control tumour growth and possibly reduce the tumour mass.

We are currently looking at drugs, already available in clinical practice or trials, which can specifically target our proteins of interest. The use of drugs that have been already approved is time and cost effective and will allow us to move quicker to clinical trials. Importantly, we won’t need to perform any drug testing on animals to examine the safety of the drug.

Our research approach allowed us to predict novel therapeutic targets and also biomarkers using the surplus tissue after surgical resection of the tumour, without any need to recreate the tumour in mice, thus saving hundreds of animals, and at the same time gaining more reliable results.

We are extremely grateful for the financial support received from AFR UK and its supporters which made this research possible. One step forward in the fight against these tumours has been made and we won’t stop until we will find a cure, this is our promise to the patients and the supporters who believed in us.

1 in 8 women in the UK will be diagnosed with breast cancer in their lifetime. In partnership with Breast Cancer UK we want to raise £90,000 to fund an innovative research project that will help us to prevent the disease in more people in the future.

We rely on our amazing fundraisers to raise funds in their community to fund our ground-breaking and innovative animal free research. Our fundraising groups across the UK are the perfect place to share fundraising and volunteering ideas, network with other supporters in your area, organise fundraising events and meet up. Find a group near you.

Related

The Home Office today announced the latest numbers on the scientific procedures performed on live animals in Great Britain in 2016. The total number of procedures performed went down from 2015 by 5% to 3.94 million procedures. This included 4,932 procedures on 3,530 dogs, 3,569 procedures on 2,440 primates. 3.87 million animals were used overall.

Stem cells are unspecialised cells that have the extraordinary potential to either proliferate through mitosis to produce more stem cells or to differentiate, under certain physiological or experimental conditions, into more specialised cells such as brain or muscle cells.

This project aims to assess the utility of induced pluripotent stem cells (iPSCs) as a relevant model system for the pre-clinical testing of novel therapies to target cancer stem cells, especially in leukaemia. Currently, scientists rely on animals, such as mice, for the early or preclinical development of novel therapies in cancer.

The project’s objectives are to replace animal use in dental research by developing a 3D model of human gums that do not involve the use of any animal products. The model should be able to closely mimic the in vivo environment and model clinical outcomes for tooth root implants in vitro.

The team aim to produce a much more realistic cell culture model of drug uptake so that fewer animal experiments are needed, with the ultimate aim being to replace these altogether. Animal experiments for drug testing range from in vitro cell assays through to assays on excised animal tissue and chronic experiments in surgically modified dogs.

Scientists from Binghamton University in the USA have developed a re-usable multi-layer microfluidic device to model the human kidney. The model incorporates a porous growth substrate, physiological fluid flow, and also allows for the passive filtration of the glomerulus.

The ARC, at the Blizard Institute QMUL, will provide a unique environment for scientists to work together to develop human-based models of skin, breast and prostate cancer, replacing mouse models. It also aims to inspire the next generation of scientists through education about animal free research.

In 2015, the number of animals used for the first time in procedures for scientific purposes was 4.07 million (4,069,349). The number of procedures that were conducted on animals is slightly higher at 4.14 million (4,142,631). These numbers, over the past few years have remained fairly similar with both the number of animals used and the number of procedures conducted hovering around the 4 million mark consistently.

With your help, we can free animals from laboratories for good.Our work is funded entirely by your generous support. Your donation helps to fund some of the most advanced and successful human-related techniques in many areas of medical research including cancer, Alzheimer's, asthma, heart and liver disease.

The use of animals in experimentation and testing in the UK is regulated under the Animals (Scientific Procedures) Act 1986, known as ASPA. This Act states the legal provisions that have been created for the protection of animals used for experimental or other scientific purposes.